Neuroprotective Effects Of Melatonin Against Hypoxic-ischemic Brain Damage In Neonatal Rats.

Objective To study the neuroprotective effects of melatonin against hypoxic-ischemic brain damage in neonatal rats and the medication time of melatonin.Methods Postnatal 7-day-old Sprague-Dawley rats were randomly divided intosix groups: sham operation group, model group (HIBD group), melatonin treated groups (according to the administration time divided into 4 groups: before HIBD, after HIBD 0 hour, after HIBD1 hour and after HIBD 2 hours ). The brains were obtained in different times after HIBD, hematoxylin-eosine staining was used to observe the tissues pathological changes, terminal deoxynucleotidyl transferase mediated dUDP-biotin nick end labeling was used to detect the apoptosis of neurons in cortex and hippocampus, immunohistochemistry was used to detect the expression of neurone specific enolase, Blood was obtained by heart puncture, the serum was detected by enzyme-linked immunosorbentassay for neurone specific enolase.Results The neuronic apoptosis in cortex and hippocampus appeared at 6 hoursafter HIBD, peaked at 24 hours, and then decreased gradually, There was a remarkable lower quantity in melatonin treated groups compared with HIBD group at 6h,12h,24h,48h and 72h (p<0.01)though there were differences among melatonin treated groups. The changes of neurone specific enolase in brain tissue and serum have significant negative correlation (r=-0.92), There is significant negative correlation(r=-0.892) between the changes of NSE in brain tissue and the neuronic apoptosis in cortex, NSE appeared at 6 hours after HIBD, peaked at 24 hours, and then decreased gradually, The activity of neurone specific enolase in melatonin treated groups has a significant difference in statistics compared with HIBD group at 6h,12h,24h,48h and 72h (p<0.01) though there were differences among melatonin treated groups. There weren't remarkable differencesin the changes of cell apoptosis and neurone specific enolase among before HIBD group, after HIBD 0 hour and after HIBD1 hour (p>0.05) , but there were significant differences between theirs and after HIBD2 hours group(p<0.01).Conclusion ? Melatonin has protective and therapeutical effects againsthypoxic-ischemic brain damage in neonatal rats. ?The changes of neurone specific enolase in serum can demonstrate the brain damage degree well. ?There is significant negative correlation(r=-0.892) between the changes of NSE in brain tissue and the neuronic apoptosis in cortex.? The neuronic apoptosis in melatonin treated groups aren't obviously so many as HIBD model group's. ?There has a time limited in using melatonin, preventive medication and medication within 2 hours after HIBD could obtain good effects, and medication within 1 hour group is better than 2 hours after HIBD.